Profiling Ssb-Nascent Chain Interactions Reveals Principles of Hsp70-Assisted Folding

Kristina Döring, Nabeel Ahmed, Trine Riemer, Harsha Garadi Suresh, Yevhen Vainshtein, Markus Habich, Jan Riemer, Matthias P. Mayer, Edward P. O'Brien, Günter Kramer, Bernd Bukau

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38 Scopus citations

Abstract

The yeast Hsp70 chaperone Ssb interacts with ribosomes and nascent polypeptides to assist protein folding. To reveal its working principle, we determined the nascent chain-binding pattern of Ssb at near-residue resolution by in vivo selective ribosome profiling. Ssb associates broadly with cytosolic, nuclear, and hitherto unknown substrate classes of mitochondrial and endoplasmic reticulum (ER) nascent proteins, supporting its general chaperone function. Ssb engages most substrates by multiple binding-release cycles to a degenerate sequence enriched in positively charged and aromatic amino acids. Timely association with this motif upon emergence at the ribosomal tunnel exit requires ribosome-associated complex (RAC) but not nascent polypeptide-associated complex (NAC). Ribosome footprint densities along orfs reveal faster translation at times of Ssb binding, mainly imposed by biases in mRNA secondary structure, codon usage, and Ssb action. Ssb thus employs substrate-tailored dynamic nascent chain associations to coordinate co-translational protein folding, facilitate accelerated translation, and support membrane targeting of organellar proteins.

Original languageEnglish (US)
Pages (from-to)298-311.e20
JournalCell
Volume170
Issue number2
DOIs
StatePublished - Jul 13 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Döring, K., Ahmed, N., Riemer, T., Suresh, H. G., Vainshtein, Y., Habich, M., Riemer, J., Mayer, M. P., O'Brien, E. P., Kramer, G., & Bukau, B. (2017). Profiling Ssb-Nascent Chain Interactions Reveals Principles of Hsp70-Assisted Folding. Cell, 170(2), 298-311.e20. https://doi.org/10.1016/j.cell.2017.06.038